New treatment for MS tested in phase 1 study
A new treatment for multiple sclerosis (MS) has demonstrated good safety and tolerability in a phase 1b study published in the journal PNAS. The treatment is based on the patients’ own red blood cells, which are used to train the immune system to tolerate substances that are mistakenly attacked in the disease. The study was conducted at University Hospital Zurich in collaboration with researchers at Karolinska Institutet.
Multiple sclerosis is an autoimmune disease in which the immune system attacks the nervous system. Current treatments can slow disease activity, but they often affect the immune system more broadly. Researchers are therefore working to develop treatments that target the immune reactions causing the disease, without affecting the rest of the immune system to the same extent.
In the current study, the researchers investigated a new method in which peptides, small protein fragments, from myelin were linked to the patients’ own red blood cells. Myelin is the protective sheath around nerve fibres that is often attacked by the immune system in MS. The aim is to create what is known as antigen-specific immune tolerance, meaning that the immune system learns not to react to these substances. The patients were monitored clinically, radiologically and through extensive immunological analyses.
Good tolerance development
The researchers found that the treatment was well tolerated, with stable clinical and MRI findings, and also observed a reduction in neurofilament light, a biomarker for tissue damage in the brain, following treatment. At the same time, the immunological analyses showed an increase in regulatory T cells and tolerogenic monocytes, which help suppress inflammation, as well as a reduction in pro-inflammatory autoreactive T cells. This highlights the treatment’s mechanism of action and is consistent with the development of tolerance.
“We were able to monitor in detail the dynamics of the pathological autoreactive immune response during treatment, which sheds light both on the treatment’s mechanism of action and on the underlying pathophysiology of MS,” says Mattias Bronge, physician and affiliated researcher at the Department of Clinical Neuroscience, and one of the KI-affiliated researchers behind the article.
As this was a phase 1 study with a limited number of participants and was not designed to evaluate treatment efficacy, the results need to be confirmed in larger studies before any conclusions can be drawn about the method’s clinical benefit.
“After more than two decades of development work, we have now overcome the first clinical hurdle in reaching patients with the treatment,” says the study’s senior author Roland Martin from UZH’s Institute of Experimental Immunology and affiliated researcher at the Department of Clinical Neuroscience, Karolinska Institutet.
Collaboration with KI
The study was carried out at University Hospital and the University of Zurich in collaboration with researchers at Karolinska Institutet and several other research institutions. The research was funded by, among others, Wyss Zurich, the European Research Council (ERC), the University of Zurich, the Swiss National Science Foundation, the Swedish Research Council, the Swedish Brain Foundation, and the Knut and Alice Wallenberg Foundation. Several of the researchers have reported patents, company affiliations, or fees from pharmaceutical companies, as disclosed in the scientific article.
Publication
"Treatment of multiple sclerosis with peptide-coupled red blood cells induces antigen-specific T regulatory cells",
Lutterotti A, Ludersdorfer T, Docampo M J, Martin R, Bronge M, Thomas O G, et al., PNAS, Online 31 August 2026, doi:10.1073/pnas.2614908123.